Hobson James J, Edwards Stephanie, Slater Rebecca A, Martin Philip, Owen Andrew, Rannard Steve P
Department of Molecular and Clinical Pharmacology, University of Liverpool Block H, 70 Pembroke Place Liverpool L69 3GF UK
Department of Chemistry, University of Liverpool Crown Street Liverpool L69 7ZD UK
RSC Adv. 2018 Apr 9;8(23):12984-12991. doi: 10.1039/c8ra01944d. eCollection 2018 Apr 3.
The delivery of drugs to the bloodstream oral administration may suffer from a number of complications including poor dissolution, first pass metabolism and the active intervention of efflux transporters such as P-glycoproteins; drugs which are efflux substrates may cause considerable problems across many clinical conditions. Here we have employed a branch-polymer stabilised nanoemulsion strategy to create highly robust oil droplets ( peanut oil, castor oil and soybean oil) containing different dissolved antiretroviral drugs used in the daily fight against HIV/AIDS. Although very limited difference in permeation through a Caco-2 gut epithelium model was seen for efavirenz, the permeation of the protease inhibitor lopinavir was considerably higher (approximately 10-fold) when applied to an epithelium monolayer in emulsion form than the control within an aqueous DMSO vehicle. The presented nanoemulsion approach may allow drug-specific permeation improvements for various drug substances.
药物进入血液循环的口服给药方式可能会出现许多并发症,包括溶解不良、首过代谢以及诸如P-糖蛋白等外排转运体的主动干预;作为外排底物的药物在许多临床情况下可能会引发相当大的问题。在这里,我们采用了一种支化聚合物稳定的纳米乳液策略,来制备含有不同溶解抗逆转录病毒药物的高度稳定的油滴(花生油、蓖麻油和大豆油),这些药物用于日常对抗艾滋病毒/艾滋病。尽管在通过Caco-2肠道上皮模型的渗透方面,依非韦伦的差异非常有限,但当以乳液形式应用于上皮单层时,蛋白酶抑制剂洛匹那韦的渗透比在水性二甲基亚砜载体中的对照高出很多(约10倍)。所提出的纳米乳液方法可能会针对各种药物实现特定药物的渗透改善。